A deep intronic recurrent CHEK2 variant c.1009-118_1009-87delinsC affects pre-mRNA splicing and contributes to hereditary breast cancer predisposition

Breast. 2024 Mar 25;75:103721. doi: 10.1016/j.breast.2024.103721. Online ahead of print.ABSTRACTGermline CHEK2 pathogenic variants confer an increased risk of female breast cancer (FBC). Here we describe a recurrent germline intronic variant c.1009-118_1009-87delinsC, which showed a splice acceptor shift in RNA analysis, introducing a premature stop codon (p.Tyr337PhefsTer37). The variant was found in 21/10,204 (0.21%) Czech FBC patients compared to 1/3250 (0.03%) controls (p = 0.04) and in 4/3639 (0.11%) FBC patients from an independent German dataset. In addition, we found this variant in 5/2966 (0.17%) Czech (but none of the 443 German) ovarian cancer patients, three of whom developed early-onset tumors. Based on these observations, we classified this variant as likely pathogenic.PMID:38554551 | DOI:10.1016/j.breast.2024.103721

Source: Breast - March 30, 2024 Category: Cancer & Oncology Authors: Petra Zemankova Marta Cerna Klara Horackova Corinna Ernst Jana Soukupova Marianna Borecka Britta Bl ümcke Leona Cerna Monika Cerna Vaclava Curtisova Tatana Dolezalova Petra Duskova Lenka Dvorakova Lenka Foretova Ondrej Havranek Jan Hauke Eric Hahnen Milo Source Type: research